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Background: Preclinical studies in transgenic models of Alzheimer’s disease (AD) suggest that DHP1401 has neuroprotective and memory-enhancing effects. Objective: To evaluate the efficacy and safety of DHP1401 in AD patients treated with donepezil Methods: Methods: In a double-blind study, patients with mild-to-moderate AD were randomized (1:1:1) to receive a twice daily total dose of 500 mg or 1000 mg DHP1401 or placebo for 24 weeks. Tolerability and safety were monitored at baseline and weeks 12 and 24. Results: total of 180 patients were randomized to Active 1 (500 mg: n = 62), Active 2 (1000 mg: n = 53), and control groups (n = 65) in 16 sites in Korea. There was no significant difference in the Alzheimer’s Disease Assessment Scale (ADAS-cog) score, the primary efficacy endpoint, from baseline. However, in the subgroup with mild AD patients (MMSE, 20–26) who received the high dose of DHP1401 and the group that received donepezil 5 mg, the ADAS-cog scores improved. MMSE and K-TMT-e type B were significant in both active groups at week 24. The most frequently observed symptom was dizziness (2.78%), and the most commonly observed reactions were related to metabolism and nutrition disorders (5.00%). No remarkable adverse events were observed for 24 weeks. Conclusion: Although the effectiveness of DHP1401 was not proved to be superior as the primary efficacy endpoint, the secondary endpoints, MMSE and K-TMT-e type B, showed significant beneficial effects. Also, the subgroups showed that ADAS-cog scores significantly were improved. DHP1401 could be proven beneficial for the AD treatment by further clinical trials.

Early detection of subjective cognitive decline (SCD) due to Alzheimer's disease (AD) is important for clinical research and effective prevention and management. This study examined if quantitative electroencephalography (qEEG) could be used for early detection of AD in SCD.Participants with SCD from 6 dementia clinics in Korea were enrolled.The present study included 95 participants aged over 65 years, including 26 amyloid PET (+) and 69 amyloid PET (-). In participants with amyloid PET (+), relative power at delta band was higher in frontal (SCD participants with amyloid PET (+) showed increased delta and decreased alpha 1 activity. qEEG is a potential means for predicting amyloid pathology in SCD. Further longitudinal studies are needed to confirm these findings.

National dementia plans were applied in dementia support centers established in Seoul, Korea between 2007 and 2009. However, the annual incidence rates of dementia in Seoul have not been reported. We investigated this annual incidence and the characteristics of incident cases from 2003 to 2018. The customized research database of the Korean National Health Insurance Services was used. The annual crude and age-standardized incidence of dementia patients and their characteristics were analyzed. This study analyzed 108,596 incident dementia cases aged ≥60 years. The incidence rate increased from 2003 to 2011, including a rapid increment from 2007 to 2011. From 2011 to 2018, the crude (age-standardized) incidence per 105 person-years decreased from 641.51 (577.12) to 448.26 (361.23). The proportion of incident dementia cases was highest in the highest income group every year. However, the proportion of incident dementia cases in the lowest income group increased from 10.4% in 2003 to 25.8% in 2011. The annual incidence rate of dementia showed a sharp increase immediately after 2007, the year dementia support centers began to be introduced, and then stabilized after 2011. The characteristics of incident dementia cases have changed, including the proportion in the low-income group.

Background and Purpose: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. Methods: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. Results: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02–0.89]). Conclusions: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01932203.

Herpesviruses affect the development of dementia. We investigated the association between herpes infection and subsequent diagnoses of dementia. Data from the National Health Insurance Service of South Korea were used. Patients aged ≥50 years with the relevant diagnostic codes in the reference year 2009 were included and prospectively reviewed from January 2010 to December 2018. All study participants were followed from the index date until the onset of dementia, death, or the study endpoint. The three cohorts comprised 92,095 patients with herpes simplex virus (HSV) infections, 97,323 patients with varicella-zoster virus (VZV) infections, and 183,779 controls. During the follow-up period, 15,831 (17.19%) subjects with HSV infection and 17,082 (17.55%) VZV-infected subjects, compared to 27,028 (14.17%) control subjects, were subsequently diagnosed with dementia (all, P.001). The adjusted hazard ratio for developing dementia was found to be 1.18 (95% confidence interval [CI]; 1.16-1.20) in HSV and 1.09 (95% CI; 1.07-1.11) in VZV patients (all, P.001). HSV1 infections such as oral or ocular subtypes, but not HSV2, anogenital subtype, were associated with dementia, including several subtypes such as Alzheimer's disease (AD), vascular dementia, and dementia with Lewy bodies. VZV infection is also associated with AD. In this Korean nationwide population-based cohort study, both HSV and VZV infections were associated with a higher risk of dementia, particularly AD. Among the subtypes of HSV infection, HSV1 is associated with a risk of dementia. Further studies including appropriate public health interventions could evaluate the causality of these relationships.

BACKGROUND Spatial navigation impairment is recognized as a potential marker of preclinical dementia. Virtual reality (VR) technology has been introduced as a promising framework for dementia research. Recent work has demonstrated further possibilities that integrating electroencephalography (EEG) sensors into VR headsets can provide invaluable information relevant to cognitive impairment. OBJECTIVE The aim of this study is to explore the feasibility of spatial navigation assessment in EEG-integrated VR devices for assessing cognitive impairment. This study will further investigate the neurophysiological characteristics of wearable EEG sensors during a VR spatial navigation game. METHODS Participants recruited for the study will be grouped into three based on their cognitive status (mild Alzheimer’s disease group, mild cognitive impairment group, and healthy controls). The spatial navigation game is designed based on the hidden goal task to assess egocentric and allocentric spatial information processing. As outcome measures, spatial navigation errors, spectral density characteristics of EEG signals, and behavioral responses in VR will be analyzed. RESULTS A spatial navigation game for VR was developed in March 2021. Recruitment commenced in June 2021. CONCLUSIONS The results of this study will provide a comprehensive understanding of VR-based spatial navigation assessment, in terms of cognitive measurement including early screening. If positive, our approach based on EEG-integrated VR devices could constitute an effective cognitive impairment screening test tool that can provide brain dynamic characteristics as well as information on spatial navigation deficits.

We conducted this meta-analysis about the effects of Souvenaid on cognition and functional abilities, with the hypothesis that Souvenaid may have beneficial effects in certain groups and the goal of finding the outcome measures, disease states, and so on, applicable for further clinical trials.We searched Medline, Embase, Web of Science, CINAHL, and the Cochrane Library. Only double- blind randomized controlled trials were included. Outcome measurements were cognition, clinical global change, functional ability, and adverse events. The duration of treatment was not restricted, but trials performed in patients who did not have Alzheimer's disease (AD) were excluded.This review using meta-analyses of 4 clinical trials showed that Souvenaid had no significant effects on cognition as measured by ADAS-Cog (MD=0.08, 95% CI=-0.71-0.88) and the neuropsychological test battery total scores (MD=0.05, 95% CI=-0,02- 0.12), on global clinical function as measured by CDR-SB (MD=-0.21, 95% CI=-0.47-0.06), or on functional ability as measured by ADCS-ADL (MD=0.36, 95% CI=-0.54-1.25). There were no differences in any adverse events (OR=0.84, 95% CI=0.63-1.12) or in serious adverse events (OR=0.95, 95% CI=0.66-1.36). However, Souvenaid may benefit the domains of cognition that are affected by AD (attention, memory, and executive function), and it may have greater potential for benefits earlier rather than later in the disease.The results of current clinical trials do not suggest that Souvenaid has any beneficial effects on cognition, functional ability, or global clinical change. Further studies with outcome measures suitable in patients with early stages of AD will be needed.

Neurofilament light chain (NfL) has been considered as a biomarker for neurodegenerative diseases including Alzheimer's disease (AD). We measured plasma NfL levels in older adults with cognitive complaints and evaluated their clinical usefulness in AD.Plasma levels of NfL, measured by using the single molecule array method, were acquired in a total of 113 subjects consisting of subjective cognitive decline (SCD; n=14), mild cognitive impairment (MCI; n=37), or dementia of Alzheimer type (DAT; n=62). Plasma NfL level was compared among three groups, and its association with cognitive and functional status was also analyzed.After adjusting for age, plasma NfL level was higher in subjects with DAT (65.98±84.96 pg/mL), compared to in subjects with SCD (16.90±2.54 pg/mL) or MCI (25.53±10.42 pg/mL,This pilot study shows that in subjects with DAT, plasma NfL levels increase. Plasma NfL level correlated with cognitive and functional status. Further longitudinal studies may help to apply the plasma NfL levels to AD, as a potential biomarker for the diagnosis and predicting progression.

Background and purpose: Poststroke cognitive impairment (PSCI) is common, but the impact of β-amyloid (Aβ) on PSCI is uncertain. The proposed study will investigate amyloid pathology in participants with PSCI and how differently their cognition progress according to the amyloid pathology. Methods: This multicenter study was designed to be prospective and observational based on a projected cohort size of 196 participants with either newly developed cognitive impairment, or rapidly aggravated CI, within 3 months after acute cerebral infarction. They will undergo 18F-flutemetamol positron emission tomography at baseline and will be categorized as either amyloid-positive (A+) or amyloid-negative (A−) by visual rating. The primary outcome measures will be based on Korean Mini-Mental State Examination changes (baseline to 12 months) between the A+ and A− groups. The secondary outcome measures will be the dementia-conversion rate and changes in the Korean version of the Montreal Cognitive Assessment (baseline to 12 months) between the A+ and A− groups. Conclusions: This study will provide a broadened perspective on the impact of Aβ on the cause and outcomes of PSCI in clinical practice. Identifying amyloid pathology in patients with PSCI will help select patients who need more focused treatments such as acetylcholinesterase inhibitors Trial registration: Clinical Research Information Service identifier: KCT0005086

Supplemental Digital Content is available in the text, Both Taiwan and Korea are developed countries with different cultures. When encountering the issue of dementia, such sociobehavioral factors have various and different impacts on dementia. We aim to assess the cross-national difference of sociobehavioral impact on cognitive preservation in Alzheimer's disease (AD) between Taiwan and Korea. A uniformed data set was administered regarding AD. We evaluated annual cognitive function using the Mini-Mental State Examination (MMSE), Clinical Dementia Rating sum of box (CDR-SB), and CDR for 2 continuous years. Annual change of scores compared with the baseline indicated cognitive change as preservation or decline. We recorded the sociodemographic variables of interest, including education duration, level of independence, living situation, and marital status. Step-wise regression analyses were performed to determine the independent factors for cognitive preservation. In total, 503 participants in Taiwan and 77 participants in Korea were recruited from 2011 to 2014. The baseline demographic characteristics were different in levels of education, living situation, level of independence, and dementia severity between the 2 countries. With follow-up for 2 years, cognitive preservation was associated with CDR staging at baseline and independence [adjusted odds ratio (OR) = 1.657, 95% confidence interval (95% CI) = 1.109–2.477, P = .014] in the Taiwanese population, whereas cognitive preservation was related to living alone (adjusted OR = 3.316, 95% CI = 1.135–9.687, P = .028) in the Korean population. The levels of education showed inconsistency in cognitive preservation in both countries. Cognitive preservation was associated with independence in the Taiwanese population, whereas cognitive preservation was related to living alone in the Korean population. By practicing relevant socioeconomic support, this might contribute to lessening the negative impact of dementia and preserving cognition in different countries.

The PDE5 inhibitors have recently been found to have cognitive-enhancing effects in animal models. To investigate the efficacy of repeated dosing with a PDE5 inhibitor on cognitive function and somatization in patients with erectile dysfunction, 27 patients with erectile dysfunction received udenafil (100 mg) at 3-day intervals for 2 months. The international index of erectile function-5 (IIEF-5), a cognitive battery (the Korean version of mini-mental state examination (K-MMSE), the frontal assessment battery (K-FAB), the Seoul verbal learning test) and a physical health questionnaire-15 (PHQ-15) were performed at baseline and at 2 months, following the administration of udenafil. The patients were divided on the basis of their IIEF-5 score into responders (change>7) and non-responders. The mean IIEF-5 score was significantly increased after treatment (7.92 ± 3.83 to 16.33 ± 4.75, P

Aim: Donepezil has not been evaluated in Korean patients with Alzheimer's disease (AD) for up to 1 year. The objectives of this study were to evaluate the differential efficacy of donepezil in Korean AD patients with and without concomitant cerebrovascular lesions (CVL). Methods: This study was a 48-week open-label trial of donepezil in patients with probable AD of mild to moderate severity. CVL were evaluated through magnetic resonance imaging (MRI) findings within 3 months. Efficacy analyses were performed for cognitive, behavioral and functional outcome measures. Results: Concomitant CVL were documented in 35 (30.7%) of the patients on MRI. Seventy-nine (69.3%) of the patients were considered not to have concomitant CVL. The mean Mini-Mental State Examination scores of both patients with and without CVL showed improvement at each evaluation. However, there was no statistical difference in improvement between the groups. Conclusion: The presence of CVL should not deter clinicians from treating AD with donepezil. Geriatr Gerontol Int 2011; 11: 90–97.

Impaired renal function is regarded as a risk factor for vascular disease, and is associated with an increasing pulse wave velocity. Both renal dysfunction and arterial stiffness are associated with cognitive impairment and dementia. However, there have been few studies that have evaluated the relationship between albuminuria and arterial stiffness and Alzheimer’s disease (AD). We investigated renal dysfunction and arterial stiffness in AD, as compared to normal controls, patients with subjective memory impairment (SMI), and patients with mild cognitive impairment (MCI). Case–control comparisons were made between 29 patients with AD, 27 with MCI, 14 with SMI, and 25 healthy controls. All patients underwent clinical and neuropsychological assessments. The urine albumin/creatinine ratio and estimated glomerular filtration rate (eGFR) were determined. Pulse wave velocity and the ankle-brachial index were used to evaluate arterial stiffness. The urine albumin/creatinine ratio and eGFR were significantly different in patients with AD, compared with the results from cognitive normal controls. The pulse wave velocity was increased and the ankle-brachial index was decreased in AD. The eGFR was well correlated with other indices and decreasing eGFR was independently associated with cognitive decline. In conclusion, albuminuria, a decreased glomerular filtration rate, an increased pulse wave velocity, and a decreased ankle-brachial index were associated with AD. These finding suggests that impaired renal functions and arterial stiffness are related to AD, in which a vascular mechanism plays a prominent role in the cognitive dysfunction associated with the disease.

This study was performed to explore the possible contributions of cerebral hemodynamic changes to the cognitive impairment in patients with Alzheimer's disease (AD).A total of 194 participants were included: 52 controls, 75 patients with mild cognitive impairment (MCI), and 67 patients with AD. Demographic characteristics, vascular risks, mini-mental state examination (MMSE), and clinical dementia rating (CDR) were assessed, and magnetic resonance imaging of the brain was performed to evaluate white matter hyperintensities (WMHs). Using transcranial Doppler (TCD) ultrasonography, cerebrovascular reactivity (CVR) was evaluated with a breath-holding test, in addition to the mean blood flow velocity (MFV), pulsatility index (PI), and resistance index (RI) of the middle cerebral artery.After adjusting for covariates such as age, education, WMH severity, and vascular risks, TCD parameters such as MFV, PI, and RI did not differ between the 3 groups. However, CVR was significantly reduced in the AD group (45.33 ± 11.49%), compared with the other groups (56.36 ± 14.65%, controls; 53.84 ± 15.47%, MCI group; P .001). Multiple regression analyses also showed that CVR was associated with MMSE scores. CVR differed according to the CDR scores (P .001).Our finding may be suggestive of an underlying microangiopathic mechanism in AD patients. Furthermore, there was an association between the impaired function of cerebral microvessels and cognitive impairment. Further research is needed to fully establish whether altered cerebral hemodynamics may be considered an independent factor in predicting cognitive decline or an effect of pathologic processes involved in AD.

ObjectiveaaComprehensive neuropsychological tests are important in the diagnosis and follow-up of patients with MCI; however, most were developed without consideration of illiteracy. We developed the Literacy Independent Cognitive Assessment (LICA) as a comprehensive neuropsychological assessment battery applicable to older adults who are either literate or illiterate. This study aimed to assess the reliability and validity of the LICA for diagnosis of MCI. MethodsaaNormal controls (n=634) and patients with MCI (n=128) were recruited from 13 centers were included in this study. Participants were divided into illiterate or literate groups, based on their performance on a brief reading and writing test. The LICA, Korean Mini-Mental State Examination (K-MMSE), and Seoul Neuropsychological Screening Battery (SNSB) were administered. ResultsaaTotal LICA scores distinguished MCI patients from controls (p

Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are well-recognized syndromes that are related to various conditions such as rapid correction of hyponatremia and chronic alcoholism. We report a very case of a patient with dysarthria, dysphagia and psychiatric symptoms including abnormal behavior starting after alcohol withdrawal, with radiological evidence of CPM and EPM. There was little improvement in the dysarthria or psychiatric symptoms in the first month.

Leukemia is a systemic disease that affects many end-organs, including those in the nervous system. It may directly affect the central or peripheral nervous systems via the production of intraparen...

other neurological symptoms such as headache, dizziness or focal weakness. There was no history of hypertension, diabetes, transient ischemic attacks, stroke, epilepsy, migraine, psychiatric illness, head trauma or alcohol abuse. On examination, the patient was alert, with a blood pressure of 130/80 mm Hg, a regular heart beat of 75 beats/min and a temperature of 36.7 ° C. Physical examination demonstrated no pathologic findings. On cognitive function evaluation, comprehension was intact and the patient was fully conscious; however, he immediately forgot what was heard and continued repetitive questioning regarding what he was doing here. Except for memory deficits, the other cognitive profiles, which included attention, praxis, language and frontal function, were normal. The patient’s amnesia and repetitive questioning gradually resolved after 6 h. The next morning, the patient was oriented and had recovered anterograde and recent retrograde memory, but not memory during the attack. Laboratory studies including complete blood cell and platelet count, erythrocyte sedimentation rate, blood electrolytes, creatinine, liver enzymes, cholesterol, triglycerides, prothrombin and partial thromboplastin time, antithrombin III-protein C and protein S activity were all normal. In addition, autoantibody screens were also normal. Neither the electrocardiogram from a 24-hour Holter monitor nor transthoracic echocardiography revealed any cardiac abnormalities. The waking surface EEG during the episode was normal. Brain Dear Sir, Transient global amnesia (TGA) is a benign neurological syndrome characterized by temporary loss of anterograde and recent retrograde memory with preserved consciousness and self-awareness; it is usually accompanied by repetitive questioning and temporal disorientation for a limited period of time [1] . In the majority of TGA cases, no cause can be identified; structural imaging is invariably normal and CSF studies are generally not performed. EEGs that have been performed during an episode have been reported to demonstrate no epileptiform abnormalities [2] . Several different causes for this syndrome have been proposed, including ischemia, migraine, epileptic seizure, venous congestion and psychological disturbances; however, there remains no consensus on the etiology [3] . Moreover, TGA associated with intracerebral hemorrhage has rarely been reported. The patient described here presented with transient amnesia resulting from a left cingulate lesion. This is of particular interest because these findings suggest that activity in the cingulate gyrus and its outflow pathways may lead to TGA.

Phosphodiesterase type 5 (PDE5) inhibitors have recently been shown to have cognitive-enhancing effects in animal models and in our previous pilot study. To investigate the efficacy of daily low-dose treatment with a PDE5 inhibitor on cognitive function, depression and somatization in patients with erectile dysfunction (ED), 8-week, double-blind, placebo-controlled study enrolled 60 male patients with ED for ≥ 3 months without cognitive impairment. Forty-nine patients completed the study. Patients were randomized to receive either daily low-dose udenafil 50 mg or placebo for 2 months. The International Index of Erectile Function-5 (IIEF-5), the Korean version of the Mini-Mental State Examination (K-MMSE) for general cognitive function and the Seoul Neuropsychological Screening Battery for comprehensive neuropsychological examination, the Physical Health Questionnaire-9 (PHQ-9) for depression and the Physical Health Questionnaire-15 (PHQ-15) for somatization were administered at baseline and at 2 months. The change in the mean IIEF-5 was significantly higher in the udenafil group than the placebo group (6.08 ± 4.72 vs 2.20 ± 3.50, P=0.008). The changes in the PHQ-9 and PHQ-15 were -2.04 ± 3.14 and -2.17 ± 2.87 in the udenafil group, and 1.20 ± 1.63 and 0.56 ± 2.48 in the placebo group (both, P0.001). The changes in the K-MMSE and Digit Span Forward were 1.25 ± 1.26 and 0.92 ± 1.02 in the udenafil group, and -0.52 ± 1.19 and -0.24 ± 1.13 in the placebo group (both, P0.001). However, there were no differences in the other neuropsychological tests. Daily dosing with a PDE5 inhibitor seems to improve cognitive function, depression and somatization, as well as erectile function, in patients with ED.

P2-111 ADAPTATED SPANISH-AMERICAN MIS VERSION. PRELIMINARY RESULTS OF ARGENTINIAN MULTICENTRIC STUDY Daniel B. Seinhart, Edith Labos, Alberto Mourino, Sofia Trojanoski, Jorge Etchepareborda, Daniel Cruz, Graciela Arguello, Diana Cristalli, Luis Camera, Hospital Italiano, Buenos Aires, Argentina; Hospital Central de San Isidro, Buenos Aires, Argentina; Centro Neurologico, Mar del Plata, Argentina; Hospital Municipal Arturo Onativia, Rafael Calzada, Argentina; Centro de Memoria, Rio Gallegos, Argentina; Hospital San Roque, Gonnet, Argentina. Contact e-mail: daniel.seinhart@ hospitalitaliano.org.ar

Several clinical studies have demonstrated that patients with essential tremor (ET) may have cognitive deficits; however, detailed neuropsychological assessments in comparison with motor tasks in patients with ET have not been reported. We conducted a prospective study to determine the correlation of cognition with age, disease duration, and motor task severity in patients with ET. Forty-seven patients with ET who underwent clinical assessment using the Fahn-Tolosa-Marin clinical rating scale and detailed neuropsychological investigation were included. Cognitive decline was significantly correlated with age at the time of examination, educational status, and tremor severity; cognitive decline however, was not related to disease duration or the presence of vascular risk factors. Multiple linear regression analysis revealed that the tremor severity was independently associated with cognitive impairment in patients with ET, regardless of age, gender, educational status, duration of ET symptoms, and vascular risk factors. Our results support the finding that the age at examination and educational status are risk factors associated with dementia in patients with ET, as with other types of dementia. In addition, the relationship between tremor severity and cognitive decline suggests there may be a pathophysiologic association between the two conditions, although the pathologic basis for dementia in the older onset ET cases requires further study.

Idiopathic normal pressure hydrocephalus (iNPH) is a reversible dementia characterized by gait disturbance, incontinence and dementia. This study investigates the neuropsychological characteristics and changes of regional cerebral blood flow (rCBF) in patients with iNPH. Ten patients who met the criteria of probable iNPH and 13 normal control subjects were evaluated. The general cognitive function and detailed neuropsychological functions were measured by K-MMSE and comprehensive neuropsychological battery. Tc-99m-ethyl cysteinate dimmer (Tc-99m-ECD) single photon emission computed tomography (SPECT) was performed to measure the rCBF and statistical parametric mapping (SPM) and statistical probabilistic brain anatomic map (SPAM) was applied to the objective analysis of SPECT data. On the neuropsychological examination, all the patients showed abnormality in memory, psychomotor speed and frontal executive function. SPM analysis of SPECT images revealed that rCBF in bilateral thalami, right prefrontal area, bilateral anterior and posterior cingulate gyri, right caudate nucleus, and left parahippocampal gyrus was significantly decreased in patients with iNPH compared to normal controls (uncorrected P

With aging, the human brain tissue undergoes degeneration and a decline in cognitive function. Diffusion tensor imaging (DTI) is a sensitive method for detecting microstructural changes of the brain white matter (WM). We examined the age-dependent, region-specific, changing patterns in microstructures of the brain. This was preformed by DTI analysis of 58 healthy volunteers from Korea. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured for each region of interest (ROI) in 22 areas. The FA and ADC values of all 22 ROIs were, respectively, compared among the age groups, by linear regression analysis and analysis of variance. With aging, the ADC values tended to increase and the FA values tended to decrease. Patterns of regional changes of the FA were divided into three subgroups. The cingulum was affected earliest with aging and the age-related WM changes show an anterior to posterior gradient acceleration throughout the decades tested. This study suggests that DTI is sensitive enough a diagnostic tool to detect subtle microstructural changes. These results show that the WM has a region-specific vulnerability to the aging process.

The “closing-in” phenomenon is defined as a tendency to draw objects as closely as possible or overlap the figures in severe cases.1 It was first described by Mayer-Gross.2 Since then, this phenomenon has been reported in patients with various brain lesions and in normal children.3-5 It frequently occurs in patients with Alzheimer’s disease (AD) and is considered a specific neurocognitive indicator of AD.1,6 Little is known about the mechanisms by which the closingin phenomenon occurs. However, several hypotheses have been proposed to explain the pathophysiology of the closingin phenomenon. Mayer-Gross2 described the phenomenon as an aspect of constructional apraxia that reflects “the fear of empty space”. In addition, de Ajuriaguerra et al.4 described the closAnatomical Correlates of the “Closing-In” Phenomenon

YongSoo Shim, M.D.*, Bora Yoon, M.D.†, Yun Jeong Hong, M.D.‡, A-Hyun Cho, M.D.*, Dong-Won Yang, M.D.* Department of Neurology*, The Catholic University of Korea, Seoul; Department of Neurology†, Konyang University College of Medicine, Daejeon; ‡Hyoja Geriatric Hospital, Yongin, Korea Background: White matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) have been considered as a reliable biomarker of small vessel damages. To evaluate the severity of WMHs, it is vital to develop reliable methods to measure the volume of WMHs. We applied open source software to measure WMH volume in the semi-automated way, and tested the reliability and validity by comparing with the commonly used qualitative rating scale. Methods: Twenty five subjects with variable WMHs were recruited. ANALYZE 10.0 was used for the image processing and volumetric measurement of WMHs. The inhomogeneity and artifacts of signal were corrected with Insight Segmentation and Registration Toolkit in ANALYZE. For the gold standard of the WMH volumetric measurement, threshold method was applied with consensus of manual editing on each slice of the MRI images by two raters. Histogram of the all slices of the Fluid Attenuated Inversion Recovery (FLAIR) MRI was generated to calculate the optimal voxel intensity of threshold, and the lowest voxel threshold was decided as the mean+1.4 SD. The volumes of WMHs were generated by multiplying the area and the thickness of each slice. Interand intrarater reliability of the semi-automated volumetric and Scheltens’methods, and the association between the individual methods were analyzed. Results: The semi-automated WMH volume at the threshold of 1.4 SD as well as the gold standard volume was well correlated with the Scheltens’ visual scale (r= 0.75, p< 0.001). The semi-automated volumetry showed the excellent intra-rater (ICC= 0.9929; 95% CI, 0.98400.9968) and inter-rater reliability (ICC= 0.9830; 95% CI, 0.9620-0.9925), superior to the Scheltens’ visual rating scale. Conclusions: The semi-automated volume measurement of the WMHs with Analyze was a valid and a reliable method to quantify subcortical white matter damages of various etiologies. Received: November 15, 2012 Revision received: March 29, 2013 Accepted: March 29, 2013

Background and PurposeaaSeveral clinical studies have demonstrated that patients with essential tremor (ET) may have cognitive deficits; however, there are no published data regarding detailed neuropsychological assessments of ET without dementia. We therefore conducted a case-control study of cognitive function in patients with ET. MethodsaaThe cohort for this study comprised 34 consecutive patients with ET without dementia and 33 age-matched controls, all of who completed a dementia-screening questionnaire and underwent a detailed neuropsychological investigation. ResultsaaSevere impairments were observed in most domains for the ET group compared to the controls, including attention, part of language function, verbal memory, and frontal executive functions. ConclusionsaaOur results support the finding that the subclinical cognitive deficits characterized by attention, verbal memory impairments, and executive dysfunction are a clinical feature of ET. In addition, our results also support the finding that age at examination and educational status are the most important risk factors associated with cognitive deficits in patients with ET. J Clin Neurol 2009;5:81-84 Key Wordsaaessential tremor, cognition, age, education.

Progressive multifocal leukoencephalopathy (PML) is a rare, serious, and usually fatal demyelinating disease that occurs predominantly in severely immunosuppressed patients. The disease is caused by the infection of oligodendrocytes with JC virus that is widely distributed as a latent infection in the general populations. PML has been described mainly in patients infected with the human immunodeficiency virus. However, other immune-suppressed patients including malignancies and organ transplants can be affected with JC virus infection. Recently it is suggested that rheumatologic diseases, including systemic lupus erythematosus (SLE)